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Commentary
General on Glaucoma and Oxidative Stress. Comments on Study Design:
“Biomarkers of Lipid Peroxidation in the Aqueous Humor of Primary Open-
angle Glaucoma Patients”
Francisco Javier Hernández-Martínez*
Hospital San Juan de Dios del Aljarafe, Bormujos, Sevilla Spain
*Corresponding author: Francisco Javier Hernández-Martínez, Hospital San Juan de Dios del Aljarafe, Bormujos, Sevilla Spain, Tel: 8602984777422; Fax:
8602984777422; E-mail: fjhernandezm@hotmail.com
Received date: May 23, 2016; Accepted date: July 20, 2016; Published date: July 25, 2016
Copyright: © 2016 Hernández-Martínez FJ. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Commentary
Glaucoma is an optic neuropathy that causes progressive changes in
the visual field and whose main known risk factor is the increased IOP
[1]. Primary open-angle glaucoma (POAG) is associated with
asymptomatic and irreversible vision loss, although its cause is
unknown, it is known that in the presence of elevated intraocular
pressure (IOP) occurs sequentially death of retinal ganglion cells by
apoptosis and optic nerve fibres in its evolution cause glaucomatous
optic atrophy and permanent loss of vision [2]. There has never been
unanimously to establish which of the two injuries, structural or
functional, it can first be detected. However, experts generally agree
that early diagnosis is critical to improving the prognosis of
glaucomatous patient.
It is true that the latest acquisitions in image analysis technology
(Optical Coherence Tomography -OCT-) have provided objective and
quantifiable data of morphological damage, in any way eliminates the
subjectivity and variability of the methods previously employed. If we
speak from the functional point of view, computerized perimetry
remains the method most commonly used scanning glaucomatous
damage worldwide. While exploring the optic disc remains the way
easier to assess the damage to the optic nerve, the great variability in
the interpretation and errors derivatives thereof, the OCT has become
critical in monitoring patients with glaucoma.
However, they are not used in clinical usually, the data obtained
from the biochemical analyses to manage the progression of glaucoma,
although molecules that have been linked to this disease through
pathogenetic processes such as inflammation, cytotoxicity, apoptosis,
vascular damage, and oxidative stress, among others. This is because
the cellular and molecular mechanisms by which the ocular
hypertension (OHT) produced in the ocular anterior segment induces
an irreducible neurodegenerative process with damage to the noble
structures of the eye posterior segment and the optical path, are yet to
be elucidated. Therefore, this has been one of the objectives of our
study, we find risk factors that can monitor the progression of
glaucoma using biomarkers easily applicable in clinical practice.
As mentioned, there is evidence in the scientific literature of the
connection between oxidative stress and POAG [3,4]. We know that
stress causes oxidative damage to biomolecules, especially lipids,
nucleic acids and proteins. Our research group has worked for the last
12 years on this subject, demonstrating metabolites increased lipid
peroxidation and decreased antioxidant enzymes superoxide dismutase
(SOD), catalase (CAT) and glutathione enzyme system (GSHPx), and
total antioxidant activity in the aqueous humor of patients with POAG,
compared to subjects in the comparison group [5-12]. Other authors
have demonstrated oxidative DNA damage in the course of glaucoma
J Eye Dis Disord, an open access journal
Hernández-Martínez, J Eye Dis Disord 2017,
2:1
Open Access
by determining the increase of 8-hydroxy-2-deoxyguanosine [5]. In
addition, oxidative damage to proteins has a complex chemistry.
Forming reactive oxygen species (ROS), such as CI2Fe/ascorbic acid,
xanthine/xanthine oxidase and H2O2, cause the appearance of many
carbonyl groups and other alterations in different proteins, and
although the mechanisms differ in each of these systems, they may also
vary due to the type of affected protein. In fact, from damaged proteins
as the protein intermediates hydroperoxides which are relatively stable
and can generate new ROS by reacting with transition metals are
generated. For example, in opacified crystal has chymotryptic activity
seen lower proteasome, which can cause the accumulation of altered
proteins as described in the lens in relation to age [13,14]. Various
methods exist for determination of oxidized proteins, which include
measurement carbonylated proteins, generated by oxidation many
amino acid side chains. This is the marker of severe protein oxidation
most used.
Furthermore, supporting the hypothesis of oxidative damage in
glaucoma patients are descriptions of an increased resistance of
aqueous humor outflow from the anterior chamber in the presence of
high levels of H2O2, intense antioxidant activity detected in the
trabecular meshwork, increased SOD activity and GSHPx in aqueous
humor of glaucoma patients and lesions that induces oxidative stress
on the trabecular meshwork [15].
As discussed above, besides the peroxides, it is also known that
isoprostanes products lipoperoxidation catalytic action of ROS on
arachidonic acid, can affect synaptic neurotransmission in the tissues
of the ocular anterior segment. Currently determining F2 isoprostanes
(due to its stability) is considered one of the best methods for
determining oxidative stress by mass spectrometry, although
determinations are also made by assaying for enzyme-linked
immunosorbent assay (ELISA). F2 Isoprostanes are compounds
containing a ring F prostane (F2 type prostaglandins) and are formed
from ROS by non-enzymatic reactions. In fact, peroxidation of
esterified arachidonic acid is produced and secreted into the
circulation. After phospholipases act before eliminated in urine as free
isoprostanes. Its half-life is very short and are prostaglandin
antagonists [16].
It described that ROS are also released in processes where activation
of polymorphonuclear occurs. These release different types of ROS that
interact with pro-metalloproteinases and activating them extracellular
matrix producing cell and tissue damage [17]. This information is
apparent that remodeling of the extracellular matrix of the trabecular
meshwork correlates with increased IOP, although this process seems
to be controlled exogenously by water-soluble antioxidants such as
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Citation: Hernández-Martínez FJ (2016) General on Glaucoma and Oxidative Stress. Comments on Study Design: “Biomarkers of Lipid
Peroxidation in the Aqueous Humor of Primary Open-angle Glaucoma Patients”. J Eye Dis Disord 2: 105.
glutathione (GSH), having been identified presence of this tripeptide
and its related iris, ciliary body and trabecular meshwork enzymes.
In addition to antioxidant enzyme (SOD, CAT, GSHPx, etc.) must
consider the importance of antioxidants that can be provided
exogenously, such as vitamins and minerals we eat with our food [18].
In recent years they have appeared different jobs relating to nutrition
and its influence on the development and progression of glaucoma. In
addition to the observational and interventional studies on the subject,
a review about vitamins and minerals, carotenoids and essential fatty
acids in relation to eye health by Brown et al., University of Oxford
(UK) confirmed that vitamins A, C and E have a protective effect on
the oxidative damage of the lens [19]. Epidemiological studies carried
out by West and Oren [20] argue that eating fruits and vegetables that
contain nutrients such as vitamins C, E and various carotenoids is
inversely related to the risk of cataracts. Anyway, keep in mind that
these studies were based on observation of consumption, and in fact
could not prove that eating these foods in the diet can actually prevent
cataracts. With regard to glaucoma, there are research groups
worldwide that have linked diet and nutritional supplementation with
the course of glaucoma [21-23].
It is difficult, from the molecular point of view addressing the role of
nutrition in the management of patients with POAG. Ramdas et al.
[23] showed that a diet with a low intake of antioxidants, particularly
retinol and vitamin B1, was associated with an increased risk of
glaucoma. Coleman et al., [24] assessed the risk of progression of
glaucoma (by analyzing photographs of the optic disc and visual field)
in 95 women diagnosed among 1155 participants in the study of
osteoporotic fractures, which the influence was studied consumption
of fruits and vegetables. The study showed less progression of
glaucoma in women who frequently ate carrots, cabbage, green leafy
vegetables and apricots, compared to those who did not. These results
are really interesting and support the interest of nutrition and
antioxidant defense system in glaucoma. Another study examined the
relationship between consumption of dietary fat and POAG, including
25199 women Health Study of US nurses and 40306 men chosen from
the Health Professionals [25] concluded that increased the proportion
of polyunsaturated fatty acids (PUFAs) w-3/w-6 appears to increase
the risk of POAG.
Our research group has studied the activity of enzymes transporters
antioxidant vitamins in patients with POAG [26-28]. Zanon-Moreno et
al. suggested that genetic factors may play a key role in the effect of the
intake of antioxidants from the diet, glaucoma. They studied first the
association between polymorphisms in key vitamins A and C and
POAG carrier proteins. They included 300 subjects (150 cases with
POAG and 150 controls) in a Mediterranean population to
determinarles plasma concentrations of vitamins C and A and
polymorphisms of a single nucleotide (SNPs) in genes related to these
concentrations of vitamins: rs176990 and rs190910 in gene 1 retinol-
binding protein (RBP1); rs1279683 rs10063949 and in and genes 1 and
2 of conveyors L-ascorbic acid Na + dependent, SLC23A1 and
SLC23A2 genes respectively). POAG group subjects had significantly
lower concentrations of vitamin C in plasma controls in association
with the SNPs associated with genes that coficican for carriers of the
vitamin. The same group analyzed the association of polymorphisms
associated with vitamin E, vitamin C and GSHPx with serum
biomarkers and the risk of POAG genes. In this study 250 cases and
250 controls with POAG also a Mediterranean population were
selected. POAG patients had significantly lower plasma levels of
vitamin E (p<0.001) and vitamin C (p<0.001) than control subjects.
J Eye Dis Disord, an open access journal
Page 2 of 3
However, activity was found in significantly higher plasma GPx
enzyme in subjects with POAG compared to controls (p<0.001). The
rs1279683 polymorphisms were also analyzed gene 2 transporter L-
ascorbic acid Na+-dependent (SLC23A2), rs6994076 in gene transfer
protein alpha tocopherol (APTT), rs737723 in gene associated protein
tocopherol (SEC14L2/TAP) gene, and the gene rs757228 glutathione
peroxidase 4(GPX4). SLC23A2 gene expression was also analyzed in a
subsample. The results show an increased risk of POAG rs1279683
polymorphism associated polymorphism rs737723 and also. Likewise,
the results also suggest a gene-gene interaction between the two
polymorphisms that significantly increases the risk of developing
POAG.
Given that in some respects there is still controversy about the
theory of oxidative stress in the development and progression of
chronic diseases, and remain unresolved many issues particularly with
regard to the sequence of events that involves the time when the ROS
formation alters the balance between pro-oxidant and antioxidant
forces for the first and start the chain reaction and cell and tissue
damage in POAG, we designed this project with the main objective to
analyze the presence biomarkers of oxidative stress, quantifying the
concentration of Malonil dialdehyde and Total antioxidant status in the
aqueous humor of a population of patients with POAG and compared
with the results obtained from a group of non-glaucomatous subjects
underwent uncomplicated cataract (considered as comparative group).
This research was designed as a study, observational, transversal,
analytical and non-experimental case control including a group of
patients diagnosed with POAG and a comparison group (not healthy
control) consisted of patients with no pathological cataract (GC). Both
groups of participants were chosen to conform to the criteria of
inclusion and exclusion defined in section Material and Methods and
require surgery because of his eye disease (glaucoma vs cataracts), as
we aim to find new risk factors for glaucoma, and therefore one of our
goals has been the identification of biomarkers of oxidative stress in
the aqueous humor, which of course can not be removed in healthy
patients on ethical issues. Our main objective has been to identify new
risk factors for the progression of glaucoma, so that they can introduce
as biomarkers applicable in ophthalmology practice and improve
monitoring of glaucomatous patient.
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